Biologic sealants comprising fibrinogen and thrombin are known. Cross-linked fibrin sealant is formed when fibrinogen and thrombin are mixed together but the formed fibrin sealant is subject to undergo enzymatic degradation with plasmin. Such sealants degrade and absorb in about 4 to 7 days, while the sealant mechanical strength and tissue bonding ability must be retained until the wound heals, which can take up to about 14 days. One method for controlling fibrin sealant enzymatic degradation has been by incorporating tranexamic acid or aprotinin into the tissue sealant formulation components. Other means have been explored for improving the strength of fibrin-based adhesive/sealants, such as incorporating collagen.
Published PCT Publication WO1999/066964 by Tammishetti et al. entitled “Carbodiimide cross-linked albumin for bioadhesives, surgical sealants, and implantable devices”, teaches a method for producing a cross-linked albumin composition for use in a bioadhesive, surgical sealant or implantable device, comprising the steps of: (a) providing an albumin preparation; (b) providing a carbodiimide preparation; and (c) mixing said albumin preparation and said carbodiimide preparation under conditions which permit cross-linking of said albumin.
U.S. Pat. No. 6,371,975 by Cruise et al. entitled “Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers” discloses a biocompatible and biodegradable barrier material is applied to a tissue region, e.g., to seal a vascular puncture site. The barrier material comprises a compound, which is chemically cross-linked without use of an enzyme to form a non-liquid mechanical matrix. The compound preferably includes a protein comprising recombinant or natural serum albumin, which is mixed with a polymer that comprises poly(ethylene) glycol (PEG), and, most preferably, a multi-armed PEG polymer.
U.S. Pat. No. 6,833,408 by Sehl, et al. issued Dec. 21, 2004 teaches a method of repairing damaged tissue in a patient comprising the steps of: placing into contact with the damaged tissue an adhesive composition comprised of (i) a hydrophilic polymer; (ii) a crosslinkable component having several nucleophilic groups; and (iii) a crosslinkable component having several electrophilic groups capable of reaction with the nucleophilic groups to form covalent bonds, wherein crosslinkable components are biocompatible and nonimmunogenic, and at least one of components is hydrophilic polymer, and cross-linking of the composition results in a biocompatible, nonimmunogenic, cross-linked matrix.
U.S. Pat. No. 7,868,123 by Khatri and Bordoloi, issued Jan. 11, 2011 and entitled “Derivatized tertiary amines and uses thereof” teaches tertiary amine intermediate and electrophilic monomers derived therefrom. The invention also relates to adhesives or sealants derived from such electrophilic moieties.
Published U.S. Patent Application No. 2008/0220047 by Sawhney et al. published Sep. 11, 2008 and entitled “Low-swelling biocompatible hydrogels” teaches surgical treatment for treating a tissue inside a vertebral column by forming a low-swelling biodegradable hydrogel in situ that is adherent to a tissue inside the vertebral column. Sawhney et al. teaches a method comprising: forming a low-swelling biodegradable hydrogel by in situ polymerization that is adherent to tissue inside a vertebral column and substantially exterior to a theca in the vertebral column, wherein the first functional groups comprise nucleophiles and the second functional groups comprise electrophiles, wherein the first synthetic precursor is selected from the group consisting of dilysines, trilysines, and tetralysines, wherein the second synthetic precursor comprises a multi-armed precursor possessing a core and arms, the arms each comprising a polyethylene glycol having a molecular weight from about 250 to about 5000, wherein the core is selected from the group consisting of polyethers, polyamino acids, proteins, and polyols, and wherein forming the hydrogel comprises reacting a first synthetic precursor comprising at least three of a first functional group with a second synthetic polymer precursor comprising at least three arms that each comprise a second functional group, wherein the first functional group reacts with the second functional group to form covalent crosslinks between the first synthetic precursor and the second synthetic polymer precursor, and wherein the hydrogel swells upon exposure to a physiological solution.
Published U.S. Patent Application No. 2007/0280988 by Ludwig et al. published Dec. 6, 2007 and entitled “Coating layers for medical devices and methods of making the same” teaches methods for controlling the morphology and the release-rate of active agent from coating layers for medical devices comprising a polymer matrix and one or more active agents. The methods comprise fixing the morphology or phase distribution of the active agent prior to removing solvent from the coating composition. The coating layers can be used for controlled delivery of an active agent or a combination of active agents.
Published U.S. Patent Application No. 2010/0173843 by Hnojewyj entitled “Tissue Adhering Compositions” discloses a method which mixes a first component, a second component, and a buffer material. The first component includes an electrophilic polymer material comprising poly(ethylene glycol) having a functionality of at least three. The second component includes a nucleophilic material comprising a natural or synthetic protein at a concentration of about 25% or less that, when mixed with the first component within a reaction pH range, cross-links with the first component to form a non-liquid, three-dimensional barrier. The buffer material includes tris-hydroxymethylaminomethane having a pH within the reaction pH range. The method applies the mixture to adhere to a tissue region.